Cytotoxic T lymphocytes (CTL) are likely to play an important role in limiting the spread of the human immunodeficiency virus (HIV) in infected individuals. An effective AIDS vaccine should therefore be capable of eliciting an HIV-specific CTL response. We will study SIV mac-specific CTL responses in rhesus monkeys as a model for HIV-specific CTL in man. We will explore issues of AIDS immunopathogenesis employing vaccinia- based technologies and the use of pox viruses as live recombinant vectors for the elicitation of protective immunity of SIV mac. Specifically, we will study: I. Assessment of cell mediated immune responses in combined vaccine trials. II. CTL in the immunopathogenesis of SIVmac-induced disease. A. Mechanisms of SIVmac escape from CTL recognition. B. Genetic basis for variation in SIVmac nef-specific CTL response. III. Novel systems for expressing AIDS virus gene products in target cells for use in CTL assays. IV. CTL induction following immunization with vaccinia-SIVmac gag-IL-2 or-IL-6. V. Novel vaccinia-based strategies for elicitation of SIV mac-specific CTL. A. Particle immunization alone in adult and new-born monkeys. B. Sequential use of two differing live vectors, vaccinia and BCG.